Laparoscopic transvesical vesicovaginal fistula repair with the least invasive way: Only three trocars and a limited posterior cystotomy.

OBJECTIVE: Two conventional approaches for vesicovaginal fistula (VVF) repair are transabdominal repair for supratrigonal VVF and transvaginal approach for low lying fistulae. Laparoscopic surgery was introduced to duplicate the surgical steps of the transabdominal approach with reduction in morbidity. We report a series of patients treated with a modified laparoscopic technique which includes the use of only three trocars and a limited posterior cystotomy. METHODS: We retrospectively reviewed the data of eight patients who underwent laparoscopic VVF repair with our standardized technique from January 2015 to April 2018. Only cases with a supratrigonal fistula were included. We constantly used only three trocars. A limited 2 cm midline posterior cystotomy was performed using ultrasonic energy. A stay suture on a straight needle was passed percutaneously in the abdomen, then on either side of the cystotomy and finally was exteriorized to maintain countertraction. The cystotomy was extended downwards to include the fistula site. The fistula was dissected circumferentially to raise the bladder and vaginal flaps. The vaginal defect was closed in a transverse fashion and the cystotomy was closed vertically. RESULTS: Mean operative time was 178±31.6 min and estimated blood loss was 60±18.7 mL. Flap interposition was performed in six cases. No intraoperative complications were recorded. Mean hospital stay was 2.25±0.89 days. During hospitalization two patients experienced postoperative complications (Clavien grade I). Mean follow-up was 20.9±11.1 months (6.0-39.0 months). All patients remained continent during the follow-up period. CONCLUSIONS: This minimally invasive laparoscopic approach with only three trocars and limited posterior cystotomy provides excellent results with minimum morbidity.

Small-angle X-ray scattering (SAXS) and nitrogen porosimetry (NP): two novel techniques for the evaluation of urinary stone hardness.

PURPOSE: To evaluate urinary stones using small-angle X-ray scattering (SAXS) and nitrogen porosimetry (NP). Traditionally, stones are categorized as hard or soft based on their chemical composition. We hypothesized that stone hardness is associated not only with its chemical composition but also with its internal architecture. SAXS and NP are well-known techniques in material sciences. We tested whether SAXS and NP are applicable for evaluating human urinary stones and whether they provide information at the nanoscale level that could be useful in clinical practice. METHODS: Thirty endoscopically removed urinary stones were studied. Standard techniques for stone analysis were used to determine the stone composition. SAXS was used to evaluate the solid part of the stone by measuring the crystal thickness (T) and the fractal dimension (Dm/Ds), while NP was used to evaluate the porosity of the stone, i.e., the pore radius, pore volume, and specific surface area (SSA). RESULTS: All stones were successfully analyzed with SAXS and NP. Each stone demonstrated unique characteristics regarding T, Dm/Ds, pore radius, pore volume, and SSA. Significant differences in those parameters were seen among the stones with almost identical chemical compositions. The combination of high T, high SSA, low Dm/Ds, low pore volume, and low pore radius is indicative of a hard material and vice versa. CONCLUSIONS: SAXS and NP can be used to evaluate human urinary stones. They provide information on stone hardness based on their nanostructure characteristics, which may be different even among stones with similar compositions.

Immunohistochemical Investigation of HER/AKT/mTOR Pathway and Cellular Adhesion Molecules in Urothelial Carcinomas.

Background. Several investigators have suggested the possibility that the expression of both EGFR and HER2 could be utilized for molecularly targeted therapy in urinary bladder cancer. We tried to evaluate the expression of HER2 and EGFR and activation of the AKT/PTEN/mTOR pathway in urothelial carcinomas and if there is any association between them and cellular adhesion molecules (CAMs). Materials and Methods. Forty-one paraffin-embedded urothelial cancer tissue blocks were collected. Immunostains for HER2, EGFR, MIB1, phospho-AKT, PTEN, phospho-mTOR, e-cadherin, p-cadherin, and b-catenin were performed on tissue microarrays sections. The immunohistochemical results were correlated with clinicopathological parameters. Results. The overexpression of HER2 was found in 19.6% of the cases and it was associated with high grade tumors with a high mitotic index and phosphorylation of AKT and mTOR. Muscle-invasive tumors presented both cytoplasmic and nuclear losses of PTEN expression. There was no association between HER/AKT/mTOR pathway activation and CAM expression. Although cadherins were often coexpressed, only p-cadherin immunoreactivity was associated with tumor grade and high proliferative index. Conclusions. HER2 overexpression is found in a respective proportion of urothelial carcinomas. P-cadherin expression is associated with high grade UCs but it is not affected by HER2 overexpression or by activation of HER/AKT/mTOR pathway.

Second-look Flexible Nephroscopy Combined With Holmium: Yttrium-Aluminum-Garnet Laser Lithotripsy Under Local Anesthesia: A Prospective Study.

OBJECTIVE: To present a prospectively studied series of patients who underwent second-look flexible nephroscopy combined with holmium:yttrium-aluminum-garnet (Ho:YAG) laser lithotripsy under local anesthesia for residual stone removal after percutaneous nephrolithotomy (PCNL). MATERIALS AND METHODS: Thirty consecutive eligible patients who underwent a PCNL procedure in the previous 48-96 hours were included. The inclusion criteria were the following: (1) 1 or 2 residual stones 0.8-1.5 cm in diameter and (2) age >18 years. Approximately 15 mL of a 2% solution of lidocaine hydrochloride was injected through the nephrostomy tube, which was then clamped for 15 minutes. Flexible nephroscopy was combined with Ho:YAG laser lithotripsy set at 0.8 Joules and 8 Hz. Patients were asked to rate their pain intensity using the numeric rating scale (NRS). RESULTS: There were 14 (46.7%) men and 16 (53.3%) women in the study, with a mean age of 45.2 ± 17.5 years. Twenty-one (70%) patients had 1 stone and 9 (30%) had 2 stones needing fragmentation. Twenty-eight (93.3%) patients successfully underwent the procedure under local anesthesia. The mean NRS value was 1.39 ± 1.08 (range 0-5). For the entire group, there was a statistically significant difference between those patients with 1 stone vs 2 stones needing fragmentation (NRS scores of 1.1 ± 0.77 vs 2.1 ± 1.36, respectively, P = .033). Operative time >30 minutes was associated with higher NRS score. The stone-free rate under local anesthesia was 86.7%. CONCLUSION: For patients with a minimal to moderate residual stone burden after PCNL, second-look flexible nephroscopy can be combined with Ho:YAG laser lithotripsy using only local anesthesia.

Tumor necrosis factor A and interleucin 6 serum values in patients undergoing extracorporeal shock wave lithotripsy for ureteral stones.

OBJECTIVE: Extracorporeal shock wave lithotripsy (ESWL) is highly effective for the treatment of uretral lithiasis and remains the first treatment option for the majority of patients when ureteral lithiasis can not be treated otherwise for more than two decades. In the present study we aim to evaluate the levels of serum tumor necrosis factor a (TNF-a) and interleucin 6 (IL-6) in patients undergoing ESWL and investigate whether preESWL levels of serum TNF-a and IL-6 correllate with any possible infectious complications after ESWL. SUBJECTS AND METHODS: Thirty patients (17 males and 13 females), with a mean age of 43 who underwent ESWL for ureteral stones and 10 healthy volunteers serving as the control group were enrolled in this study. Serum samples for TNF-a and IL-6 were obtained before ESWL and after ESWL, 1, 24, and 48 hours and 2, 24, and 48 hours, respectively. The preESWL and postESWL serum TNF-a levels and IL-6 were compared and correlated with possible tissue damage and infectious complications. RESULTS: We found that serum TNF-a levels were significantly decreased one hour (P<0,001) and increased 24 hours (P=0.007) after ESWL. Furthermore IL-6 was also significantly increased 2 hours (P<0,001), 24 and 48 hours after ESWL (P=0,003 and 0,002 respectively). In 3 patients we observed fever (39 (o)C) postESWL procedure with negative urine culture and high serum values of TNF-a and IL6 preESWL. IN CONCLUSION: A high specific markers such as serum TNF-a levels (15-25pg/ml) and IL-6 (25-35pg/ml) might be useful to identifying patients with possible infection following ESWL lithotripsy. However, further studies are needed to get more accurate results.

Can tumor necrosis factor a (TNF-a) and interleukin 6 (IL-6) be used as prognostic markers of infection following ureteroscopic lithrotripsy and extracorporeal shock wave lithotripsy for ureteral stones?

OBJECTIVE: Ureteroscopic lithotripsy (URS) and Extracorporeal shock wave lithotripsy (ESWL) are highly effective for the treatment of uretral lithiasis and remain the treatment option for the majority of patients for more than two decades. In the present study we aimed to evaluate the levels of serum tumor necrosis factor A (TNFa) and interleucin 6 (IL6) in patients undergoing ESWL and URS. SUBJECTS AND METHODS: A total number of seventy patients were involved in our study. Thirty patients (17 males, 13 females), with a mean age of 43 had underwent ESWL and thirty patients (19 males, 11 females), with a mean age of 47 (range: 26-68) underwent URS lithotripsy. Ten healthy volunteers serving as the control group were enrolled in this study. Serum samples for TNF-a and IL-6 were obtained before URS and ESWL and after the procedure at 1, 24, and 48 hours and at 2, 24, and 48 hours, respectively. The pre ESWL/URS and post ESWL/URS levels were compared and correlated with possible tissue damage. According to ESWL procedure we found that serumTNF-a levels were significantly increased after one hour (P<0,001) and after 24 hours (P=0.007). Furthermore, IL-6was significantly increased at 2 (P< 0,001), 24 and 48 hours post ESWL (P=0,003 and 0,002) respectively. For URS serum TNF-a levels were statistical significantly correlated preoperatively with one hour (P=0,0083) and 48 hours (P<0,001) after URS and IL-6 with 2 and 24 hours (P<0,001). In 3 patients for URS and 1 for ESWL we observed post procedure fever (>38.5C(o)). All those patients had preoperatively high values of TNF-a and Il-6 that increased at 1 and 2-hours respectively. In conclusion, high pre ESWL/URS levels of serum TNF-a and IL-6 may indicate a predisposition for post ESWL/URS inflammation and infection following URS lithotripsy or ESWL procedure.

Radiological findings and the clinical importance of megacalycosis.

OBJECTIVE: To describe the radiological findings and the clinical importance of megacalycosis. MATERIALS AND METHODS: On the basis of a case report and literature review, diagnostic criteria and clinical significance of megacalycosis are presented. RESULT: Megacalycosis is mostly asymptomatic and is usually discovered either accidentally or as a result of its complications, such as stone formation, flank pain, hematuria, infection, and fever. The renal pelvis, infundibulum, and ureter are not dilated. Calyces have a semilunar configuration rather than the conventional triangular or conical form. The tip of each pyramid is flat, and the calyces possess neither fornix nor papillae impressions. The number of calyces is increased compared to the healthy condition, typically from 20-25. The renal parenchyma has a normal width but with a slight narrowing of the renal medulla. The kidney exhibits normal function, in particular with respect to its ability to concentrate the urine. CONCLUSION: Megacalycosis is a rare, usually unilateral dilatation of the kidney calyces in the presence of a normal, undilated renal pelvis and ureter. Its pathological significance lies in the occurrence of complications.

Perioperative prostate specific antigen levels among coronary artery bypass grafting patients: Does extracorporeal circulation and body temperature induce prostate specific antigen levels alterations?

PURPOSE: The purpose of this study is to compare the perioperative total prostate specific antigen (tPSA) levels among coronary artery bypass grafting (CABG) patients with and without extracorporeal circulation (ECC), to investigate the changes overtime of tPSA in each group separately and to determine the effect of body core temperature on tPSA levels. MATERIALS AND METHODS: A prospective study was conducted. Our sample was allocated to: (a) Seven patients who underwent off pump CABG (Group I) and (b) 16 CABG patients with ECC (Group II). The levels of tPSA were measured preoperatively (baseline), intra-operatively and at the 4(th) postoperative day. We compared the two groups on their tPSA levels and we investigated the changes of tPSA overtime in each group separately. RESULTS: Intra-operative serum samples were obtained in significantly lower body temperature in patients of Group II than in those of Group I (31°C vs. 36.9°C, P < 0.001). In each group separately, postoperative tPSA levels were increased significantly compared to the baseline values (2.55 ng/ml vs. 0.39 ng/ml for Group I, P = 0.005 and 4.36 ng/ml vs. 0.77 for Group II, P < 0.001). CABG patients with ECC had significantly lower intra-operative tPSA levels than the baseline values (0.67 ng/ml vs. 0.77 ng/ml, P = 0.008). We did not observe significant differences of tPSA levels between the two groups. CONCLUSIONS: CABG surgery affects similarly the perioperative tPSA independently the involvement of ECC. Although all patients had significantly higher early postoperative tPSA levels, only those who underwent CABG with ECC had exceeded normal values and significantly decreased intra-operative tPSA. Hypothermia seems to be the causal factor of tPSA reduction.

Simultaneous laparoscopic management of ureteropelvic junction obstruction and renal lithiasis: the combined experience of two academic centers and review of the literature.

INTRODUCTION: Approximately one out of five patients with ureteropelvic junction obstruction (UPJO) present lithiasis in the same setting. We present our outcomes of simultaneous laparoscopic management of UPJO and pelvic or calyceal lithiasis and review the current literature. METHODS: Thirteen patients, with a mean age of 42.8±13.3 years were diagnosed with UPJO and pelvic or calyceal lithiasis. All patients were subjected to laparoscopic dismembered Hynes-Anderson pyeloplasty along with removal of single or multiple stones, using a combination of laparoscopic graspers, irrigation, and flexible nephroscopy with nitinol baskets. RESULTS: The mean operative time was 218.8±66 minutes. In two cases, transposition of the ureter due to crossing vessels was performed. The mean diameter of the largest stone was 0.87±0.25 cm and the mean number of stones retrieved was 8.2 (1-32). Eleven out of 13 patients (84.6%) were rendered stone-free. Complications included prolonged urine output from the drain in one case (Clavien grade I) and urinoma formation requiring drainage in another case (Clavien grade IIIa). The mean postoperative follow-up was 30.2 (7-51) months. No patient has experienced stone or UPJO recurrence. CONCLUSION: Laparoscopy for the management of UPJO along with renal stone removal seems a very appealing treatment, with all the advantages of minimally invasive surgery. Concomitant renal stones do not affect the outcome of laparoscopic pyeloplasty, at least in the midterm. According to our results and the latest literature data, we advocate laparoscopic management as the treatment of choice for these cases.

Can Tumor Necrosis Factor- α and Interleukin-6 Be Used as Prognostic Markers of Infection following Ureteroscopic Lithotripsy?

Introduction. Ureteroscopic lithotripsy (URS) although highly effective for the treatment of ureteral stones is associated with certain complications, the more common of which are postoperative fever and infection. In the present study we aimed to evaluate the levels of serum cytokines in patients undergoing ureteroscopic lithotripsy and investigate any possible correlation between levels of cytokines and infectious complications after URS. Materials and Methods. Thirty patients (19 males, 11 females), with a mean age of 47 (range: 26-68) that underwent URS lithotripsy for ureteral stones, and 10 healthy volunteers serving as the control group were enrolled in this study. Serum samples for TNF- α and IL-6 were obtained before surgical intervention and after 1, 24, and 48 hours and 2 , 24, and 48 hours, respectively. The preoperative and postoperative levels were compared and correlated with the possible complications after URS. Results. Serum TNF- α levels were statistically significant, increased 1 hour (P = 0.0083) and 48 hours (P < 0.001) after operation. IL-6 levels were found statistically significant, elevated after 2 and 24 hours from the URS (P < 0.001). In 2 patients we observed postoperative fever (>38.5°C). These two patients had high preoperative values of TNF- α and IL-6 ( 30 and 50 pg/mL, resp.) and these values increased postoperatively. Conclusion. High preoperative levels of serum TNF- α and IL-6 may indicate a predisposition for postoperative inflammation and infection following URS lithotripsy.

Metastatic Mucinous Adenocarcinoma of the Prostate with PSA Value of 8.6 ng/mL at 5-Year-Followup after Prostatectomy, Radiotherapy, and Androgen Deprivation.

Introduction. Mucinous adenocarcinoma of the prostate is a rare variant of prostate cancer. Its malignant potential and the clinical course of the affected patients remain, by and large, controversial. No data exist about the course of metastatic mucinous adenocarcinoma of the prostate. Case Presentation. This case report describes the excellent clinical course of a 68-year-old patient with metastatic mucinous adenocarcinoma of the prostate, treated by radical prostatectomy, irradiation, and androgen deprivation. Conclusion. In our case, mucinous adenocarcinoma of the prostate does not appear to behave differently than acinar prostate cancer. Its malignant potential is dependent on its Gleason score.

The use of a perimeatal-based penile skin flap to cover the repair of a tubularized incised plate urethroplasty: from experimental surgery to clinical practice.

OBJECTIVE: To prospectively evaluate the efficacy and safety of a perimeatal-based penile skin flap for neourethral coverage after repair of distal hypospadias with tubularized incised plate urethroplasty (TIPU). METHODS: In 12 New Zealand white rabbits a ventral urethral defect was created and reconstruction was accomplished with continuous suture. An epithelialized defect-based flap was harvested from the penile skin to cover the repaired defect. The animals were euthanized on the 28th postoperative day and their penises were processed for microscopic examination. In 32 children with distal hypospadias a TIPU was performed. A penile skin flap was created immediately below the distal end of the neourethra and used to cover the urethroplasty. RESULTS: Histological examinations revealed complete restoration of continuity of the stratified squamous epithelium without evidence of inflammation or fistula formation with full consistency with the underlying papillary reticular and corium. There were no cases of fistula formation. One patient developed meatal stenosis. All patients had a satisfactory cosmetic appearance and excellent functional results. CONCLUSION: The formation of a perimeatal-based skin flap is a simple and safe method of providing additional cover for the constructed neourethra after TIPU, minimizing the fistula rate.

Serum cytocines values in patients after endoscopic surgery for ureteral lithiasis.

Obstructive uropathy due to ureteral stones can cause renal infection and, if left untreated, can cause impairment of renal function. Endoscopic surgery such as ureteroscopy (URS) and laser lithotripsy are the primary therapeutic approach. Cytokines as non invasive markers may have a role to diagnose ureteral damage and infection. We aimed to evaluate serum cytokine levels of tumor necrosis factor-a (TNFa) and interleukin-6 (IL6) in patients undergoing URS and holmium laser lithotripsy. The study included 40 patients (male 25 and 15 female) with a mean age of 47 years and 10 healthy blood donors serving as the control group. None of them had any additional systemic diseases, previous insertion of a ureteral double "j" stent or of a nephrostomy tube, neoplasmatic disease ot renal insufficiency. Routine urine examination and urine culture were obtained to exclude urinary infection. Preoperatively and 1h, 2h, 24h and 48h postoperatively serum samples of TNF-a and IL-6 were collected and measured. Serum TNFa and IL-6 values were correlated with the other variables measured from blood samples after the URS using paired samples Students t-test with confidence interval 95%. A P value of less than 0.01 was considered statistically significant. Correlation between serum TNF-a and IL6 levels with healthy donors were statistically significant in 1h (0.004), 2h (0.001), 24h (0.001) and 48h (0.001 and 0.001) postoperatively, respectively. In conclusion, our study shows that cytokines could be helpful as markers of renal tissue damage. However, further studies are needed to get more accurate results.

Ureteroscopic laser treatment of upper urinary tract urothelial cell carcinomas: can a tumour free status be achieved?

Introduction. In cases of anatomic or functional single kidney with urothelial tumours of the upper urinary tract, the endoscopic laser ablation has proven efficacious. Based on the knowledge that low-grade, low-stage upper tract transitional cell carcinomas rarely progress to invasive lesions, indications for endoscopic laser ablation have expanded to include patients with bilateral functioning kidneys and low-grade tumours. The question that remains to be answered is whether endoscopic laser ablation has the ability to completely eradicate upper urinary tract tumours. Methods. We performed in 25 patients in a period of 11 years 288 ureteroscopies and, if needed, laser ablation of upper urinary tract tumours in imperative indication. Results. In 32% of the patients the cancer remained even after several laser sessions. 64% of patients were tumour free after one or more laser sessions but remained clear only for the next 3 months. Only 1 patient was tumour free for a period of 68 months after 1 session of laser treatment. The procedure had low complication rates. Conclusion. The laser technology and the introduction of small diameter semirigid and flexible ureteroscopes made ablation of upper urinary tract tumours possible and safe. Nevertheless a complete resection of the carcinomas is rarely possible.

Epidural anesthesia followed by epidural analgesia produces less inflammatory response than spinal anesthesia followed by intravenous morphine analgesia in patients with total knee arthroplasty.

BACKGROUND: Anesthesia and inflammatory response have been studied in major abdominal and thoracic surgical procedures, but not in major orthopaedic reconstructive procedures such as total knee arthroplasty. Most studies have compared general anesthesia with epidural anesthesia, but none has compared epidural with spinal. MATERIAL/METHODS: In a prospective randomized study, 2 groups of patients scheduled for total knee arthroplasty for osteoarthritis were evaluated regarding the inflammatory response to 2 types of regional anesthesia. In 30 patients (Group A) with spinal anesthesia followed by intravenous morphine analgesia, and in 26 patients (Group B) with epidural anesthesia followed by epidural analgesia, the inflammatory response was assessed through the calculation of leucocyte concentration (WBC), C-reactive protein (CRP), monocyte chemotactic protein 1 (MCP-1), interleukins (IL-1, IL-6, IL-10, IL-18), TNF-a, and leucocyte activation molecules CD11b and CD62l, in 3 blood samples (immediately before induction to anesthesia, immediately after closure of the operative wound, and at 24 hours post-operatively). RESULTS: The MCP-1 values showed a statistically significant increase (p<0.02) in the group of patients with spinal anesthesia. Of the leucocyte activation molecules, a high statistically significant increase was noticed in the expression of CD11b on monocytes in the sample taken 24 hours post-operatively in the patients of group A. Similarly, CD62l expression on neutrophils showed a high statistically significant reduction in the sample taken 24 hours post-operatively in the group of patients with spinal anesthesia compared to the group of patients with epidural anesthesia. CONCLUSIONS: Our results show that epidural anesthesia followed by epidural analgesia produced less inflammatory response compared with spinal anesthesia followed by intravenous morphine analgesia in patients operated on with total knee arthroplasty, and that the most sensitive markers of those investigated were the CD11b and CD62l leucocyte activation molecules.

Patterns of autophagy in urothelial cell carcinomas--the significance of "stone-like" structures (SLS) in transurethral resection biopsies.

OBJECTIVES: To investigate the microtubule-associated protein LC3A, presumed to reflect autophagic activity, in urothelial cell carcinomas (UCC) for its relevance with muscle invasion in transurethral resection (TUR) biopsies. The LC3A antibody is specific for identifying the autophagy-related protein Atg8 and, hence, autophagy-a self-degradation mechanism by which cells recycle their own cytoplasmic constituents, providing with additional energy the rapidly proliferating cells. METHODS: The study comprised 210 TUR specimens of UCC of the urinary bladder: 70 low-grade non-muscle-invasive (NMI, group A), 70 high-grade NMI (group B), and 70 high-grade muscle invasive tumors (group C). These, together with 40 controls, were stained for Atg8/LC3 using an automated immunohistochemical technique. RESULTS: The LC3A was detected as diffuse cytoplasmic staining, and as dense, spheroidal, "stone-like" structures (SLS) of variable size (1.2-12.0 µm in diameter), typically enclosed within cytoplasmic vacuoles. The LC3A reactivity, whether expressed in the form of SLS or as diffuse cytoplasmic staining, was higher in high-grade UCC than in low-grade disease and, more importantly, it was associated with muscle invasion. The median number of SLS per optical field, per section was 17.0, 19.0, and 37.0 for groups A, B, and C, respectively (A, B vs. C P < 178> 0.0001; A vs. B P = 0.27). The median SLS diameter was 4.9, 5.3, and 9.3 µm for groups A, B, and C respectively (A, B, vs. C P < 0.0001; A vs. B P = 0.03). CONCLUSION: It appears that the LC3A protein is closely connected with muscle invasion, but whether this finding is of clinical value in TUR specimens lacking muscularis propria remains to be proven.

Mismatch repair hMSH2, hMLH1, hMSH6 and hPMS2 mRNA expression profiles in precancerous and cancerous urothelium.

Changes in the expression of the mismatch repair (MMR) genes hMSH2, hMLH1, hMSH6 and hPMS2 reflect dysfunction of the DNA repair system that may allow the malignant transformation of tissue cells. The aim of the present study was to address the mRNA expression profiles of the mismatch DNA repair system in cancerous and precancerous urothelium. This is the first study to quantify MMR mRNA expression by applying quantitative real-time PCR (qPCR) and translate the results to mRNA phenotypic profiles (r, reduced; R, regular or elevated) in bladder tumors [24 urothelial cell carcinomas (UCCs) and 1 papillary urothelial neoplasm of low malignant potential (PUNLMP)] paired with their adjacent normal tissues (ANTs). Genetic instability analysis was applied at polymorphic sites distal or close to the hMSH2 and hMLH1 locus. Presenting our data, reduced hMSH2, hMSH6 and hPMS2 mRNA expression profiles were observed in cancerous and precancerous urothelia. Significantly, the ANTs of UCCs revealed the highest percentages of reduced hMSH2 (r(2)), hMSH6 (r(6)) and hPMS2 (p(2)) mRNA phenotypes relative to their tumors (P<0.03). In particular, combined r(2)r(6) (P<0.02) presented a greater difference between ANTs of low-grade UCCs vs. their tumors compared with ANTs of high-grade UCCs (P= 0.000). Reduced hMLH1 (r(1)) phenotype was not expressed in precancerous or cancerous urothelia. The hMSH6 mRNA was the most changed in UCCs (47.8%), while hMSH2, hMLH1 and hPMS2 showed overexpression (47.8, 35 and 30%, respectively) that was associated with gender and histological tumor grading or staging. Genetic instability was rare in polymorphic regions distal to hMLH1. Our data reveal a previously unrecognized hMSH2 and hMSH6 mRNA combined phenotype (r(2)r(6)) correlated with a precancerous urothelium and show that hMLH1 is transcriptionally activated in precancerous or cancerous urothelium. In the present study, it is demonstrated that reduction of hMSH6 mRNA is a frequent event in bladder tumorigenesis and reflects a common mechanism of suppression with hMSH2, while alterations of hMSH2 or hMLH1 mRNA expression in UCCs does not correlate with the allelic imbalance of polymorphic regions harboring the genes.

Postoperative pelvic hypofractionated accelerated radiotherapy with cytoprotection (HypoARC) for high-risk or recurrent prostate cancer.

AIM: We evaluated the feasibility and efficacy of postoperative hypofractionated and accelerated radiotherapy supported with amifostine cytoprotection (HypoARC) in patients with high-risk or recurrent prostate cancer. PATIENTS AND METHODS: Fourty-eight patients were recruited (median follow-up=41 months; range=12-84 months). Twenty-one received HypoARC after surgery and 27 at biochemical relapse. Radiotherapy was given with a 3D-conformal technique, delivering 2.7 Gy/day to the pelvis and 3.4 Gy to the peri-prostatic region for 14 fractions. A 15th fraction increased the total dose to the peri-prostatic area to 51 Gy (15×3.4 Gy) in 19 days. Amifostine was delivered before each radiotherapy fraction at an individualized (by tolerance) dose (0-1000 mg). RESULTS: Amifostine was delivered subcutaneously at 1000 mg in 35/48 (72.9%) patients, while lower doses were tolerated by the remaining patients. Twenty-six (54.2%) patients accomplished therapy without delays, while acute toxicities enforced 1 to 2 week delays in 11/48 patients (22.9%). Grade 2 proctitis was noted in 18.7%, while substantial bleeding occurred in 8.3% of patients. Grade 1 dysurea was noted in 27.1%, while diarrhea grade 2 appeared in 10.4% of patients. High amifostine dose was linked to a significant reduction of proctitis (p=0.04). No severe late toxicities were noted. Within a median of 41 months, 7/48 (14.6%) patients exhibited post-radiotherpy biochemical failure (in four due to metastasis). High-dose (1000 mg) amifostine defined a significantly better outcome (p=0.004), an effect sustained on multivariate analysis. CONCLUSION: Postoperative HypoARC is feasible with low-grade early and late toxicities, and emerges as a candidate for evaluation in randomized trials. The three-fold reduction of the overall treatment time renders HypoARC appealing for busy radiotherapy departments.

Laparoscopic transvesical resection of an en bloc bladder cuff and distal ureter during nephroureterectomy.

OBJECTIVE: The most appropriate technique for excising the distal ureter and bladder cuff during laparoscopic nephroureterectomy is still debated. We report our experience with a pure laparoscopic transvesical method that duplicates the long-standing open transvesical approach. MATERIALS AND METHODS: Seven men and three women diagnosed with upper tract transitional cell carcinoma were treated with this procedure. Three intravesical ports were inserted, and pneumovesicum was established at 12 mmHg. Transvesical laparoscopic circumferential detachment of the bladder cuff and en bloc mobilization of the last centimeters of the distal ureter were performed, followed by the closure of the bladder defect. Subsequently, a nephrectomy was performed either laparoscopically or using an open flank approach. RESULTS: The median age was 68.5 years. The procedure was completed uneventfully in all cases. The median operating time for distal ureter excision was 82.5 minutes (range 55-120). No complications directly related to the pneumovesicum method were recorded. The median follow-up period was 31 months (range 12-55). During the follow-up period, two patients (20%) died from the disease, and a bladder tumor developed in three cases (30%). CONCLUSION: The laparoscopic transvesical resection of the en bloc bladder cuff and distal ureter is a reliable, effective, and oncologically safe technique, at least in the midterm.